The process of membrane fusion is fundamental to cellular organization and has been the focus of a vast literature. Südhof and Rothman review the role of so-called SNARE and SM proteins in membrane fusion and present a hypothesis for how they are regulated by other proteins, termed grapples, exemplified by complexin. Two further papers also shed light on complexin’s role in regulating SNARE-mediated membrane fusion. Giraudo et al. show that a structural motif within complexin appears to act as a molecular switch directly interacting with SNAREs during membrane fusion. Maximov et al. confirm that, in neuronal systems, complexin can play a negative or positive role in SNARE-mediated membrane fusion during neurotransmitter release, potentially either clamping SNARES to prevent spontaneous fusion or promoting fusion when appropriate.